Table 2.

Definition of outcome measures

Outcome	Criterion	Definition
Primary
Hyperchloremia	Increase in serum chloride ≥ 5 mmol/L	- Difference from baseline level to the highest chloride level measured within 48 h post-randomization - Baseline level: measured on blood gas at randomization or using the closest lab or blood gas value up to a maximum of 12 h before randomization - Highest chloride level: obtained in the first 48 h post-randomization - Patients will be assumed to have no hyperchloremia if chloride has not been measured in the first 48 h post-randomization
Secondary (clinical)
Organ dysfunction free survival	Survival free of organ dysfunction	- Organ dysfunction defined by Paediatric Logistic Organ Dysfunction 2 Score – PELOD-2) [19] - A PELOD-2 score of > 0 indicates organ dysfunction - Censored at 28 days post-randomization - Assume PELOD-2 is zero at discharge from PICU in survivors - PELOD-2 calculated using the worst values of individual components each day until discharge - If a certain variable (such as creatinine) was not measured on a given day, it is assumed to be normal [19]
Acute kidney injury (AKI)	New-onset AKI	- AKI defined as per KDIGO 2012 criteria using serum creatinine values [20] - Includes AKI within the first 7 days post-randomization if not present on admission. Serum creatinine values measured in the first 7 days post-randomization will be used to assess AKI as per KDIGO 2012 criteria - Baseline creatinine: closest serum creatinine value prior to randomization, up to 12 h before randomization - Predicted baseline creatinine: for children <1 year, the reported predicted creatinine values by Boer et al. will be used, whilst for children >1 year, the below formula will be employed [21]. Mean creatinine (micromol/L) = − 2.37330 − 12.91367 * loge (age) + 23.93581 * (age)1/2 [22] Presence of AKI on admission: For those with baseline creatinine: - Baseline creatinine ≥ 1.5 times predicted baseline creatinine for those with baseline creatinine For those without baseline creatinine: - Patients will be assumed to have no AKI on admission New onset AKI: For those with baseline creatinine: - New-onset AKI will be according to KIDIGO 2012 criteria using follow-up creatinine values. If no follow-up creatinine available, these patients would be deemed to have no AKI For those without baseline creatinine: - Predicted baseline creatinine value will be calculated and assumed to be the baseline value. This value will be compared to the follow-up value (where available) as per KDIGO 2012 criteria. Where no follow-up value is available, these patients would be deemed to have no AKI.
Length of stay	Length of stay	- Length of stay in PICU from randomization to discharge - Length of stay in hospital from randomization to discharge
Survival	PICU free survival	- Censored at 28 days from the post-randomization - Patients will be assumed to be alive once discharged from PICU - For patients who die within 28 days, are discharged to a hospice or for palliative care, this value will be recorded as zero
Secondary safety outcomes, defined as serum electrolyte/metabolite abnormalities present from randomization to 48 h post-randomization
Adverse event	Hyperkalaemia	- Serum potassium > 6.2 mmol/L
	Hypokalaemia	- Serum potassium < 2.5 mmol/L
	Hypercalcaemia	- Serum corrected total calcium > 3.1 mmol/L
	Hypocalcaemia	- Serum corrected total calcium < 1.6 mmol/L
	Hypermagnesaemia	- Serum magnesium > 1.4 mmol/L
	Hyponatraemia	- Serum sodium < 125 mmol/L
	Hyperlactataemia	- Arterial or venous blood gas lactate > 4 mmol/L
	Death in hospital	- Number of deaths

Legend: PICU paediatric intensive care unit, AKI acute kidney injury, KDIGO Kidney Disease: Improving Global Outcomes, PELOD-2 Paediatric Logistic Organ Dysfunction 2 Score